Functionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1.

Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges emerged as real-life stress tests for computational hit-finding strategies. In CACHE Challenge #1, 23 participants contributed their original workflows to identify small-molecule ligands for the WD40 repeat (WDR) of LRRK2, a promising Parkinson's target. We applied the FRASE-based hit-finding robot (FRASE-bot), a platform for interaction-based screening allowing a drastic reduction of the explorable chemical space and a concurrent detection of putative ligand-binding sites.

Use of reference markers in the speech of people with schizophrenia spectrum disorders: Evidence from two referential communication tasks manipulating common ground with the interaction partner.

Introduction: People with schizophrenia spectrum disorders present with language dysfunctions, yet we know little about their use of reference markers (indefinite markers, definite markers, pronouns or names), a fundamental aspect of efficient speech production.

Methods: Twenty-five (25) participants with a recent-onset schizophrenia spectrum disorder (SZ) and 25 healthy controls (HC) completed two referential communication tasks. The tasks involved presenting to an interaction partner a series of movie characters (character identification task) and movie scenes composed of six images (narration task).

Long-Term Post-Stroke Cognition in Patients With Minor Ischemic Stroke is Related to Tract-Based Disconnection Induced by White Matter Hyperintensities.

Over a third of minor stroke patients experience post-stroke cognitive impairment (PSCI), but no validated tools exist to identify at-risk patients early. This study investigated whether disconnection features derived from infarcts and white matter hyperintensities (WMH) could serve as markers for short- and long-term cognitive decline in first-ever minor ischemic stroke patients. First-ever minor ischemic stroke patients (NIHSS ≤ 7) were prospectively followed at 72-h, 6 months, and 36 months post-stroke with cognitive tests and brain MRI.

Altered medial temporal lobe subregion volumes in systemic lupus erythematosus patients with neuropsychiatric symptoms.

Background: Systemic lupus erythematosus (SLE) often presents with neuropsychiatric (NP) involvement, including cognitive impairment and depression. Past magnetic resonance imaging (MRI) research in SLE patients showed smaller hippocampal volumes but did not investigate other medial temporal lobe (MTL) regions. Our study aims to compare MTL subregional volumes in SLE patients to healthy individuals (HI) and explore MTL subregional volumes in relation to neuropsychiatric SLE (NPSLE) manifestations.

Effect of siponimod on retinal thickness, a marker of neurodegeneration, in participants with SPMS: Findings from the EXPAND OCT substudy.

Background: People with MS show abnormal thinning of the retinal layers, which is associated with clinical disability and brain atrophy, and is a potential surrogate marker of neurodegeneration and treatment effects.

Objective: To evaluate the utility of retinal thickness as a surrogate marker of neurodegeneration and treatment effect in participants with secondary progressive MS (SPMS) from the optical coherence tomography (OCT) substudy of the EXPAND Phase 3 clinical trial (siponimod versus placebo).

Methods: In the OCT substudy population (n = 159), treatment effects on change in the average thickness of the retinal layer, peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (GCIPL) were analyzed by high-definition spectral domain OCT at months 3, 12, and 24.

Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer's Dementia.

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.

Methods: Participants were drawn from the population-based HELIAD cohort.

Blood immunophenotyping of multiple sclerosis patients at diagnosis identifies a classical monocyte subset associated to disease evolution.

Introduction: Myeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes.

Methods: Combination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing.

Results: Myeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis.

Diagnostic impact of DNA methylation classification in adult and pediatric CNS tumors.

Over the past decade, neuropathological diagnosis has undergone significant changes, integrating morphological features with molecular biomarkers. The molecular era has successfully refined neuropathological diagnostic accuracy; however, a substantial number of CNS tumor diagnoses remain challenging, particularly in children. DNA methylation classification has emerged as a powerful machine learning approach for clinical decision-making in CNS tumors.

Twelve barriers to COPD diagnosis in France: a comparative qualitative study.

Background: Chronic obstructive pulmonary disease (COPD) is a common treatable disease often diagnosed in patients with risk factors after a prolonged period with suggestive symptoms. Our qualitative study aimed to identify barriers to establishing diagnosis in the natural history of this condition.

Methods: An inductive thematic analysis was performed on structured interviews with patients, general practitioners (GPs) and pulmonologists in France.

The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant.

Background: Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, has been newly defined in the 2021 WHO classification of central nervous system tumors. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors.

Methods: We retrospectively assembled a cohort of 114 patients (median age 22 years) with diffuse hemispheric glioma, H3 G34-mutant, CNS WHO grade 4 and profiled the imaging, histological and molecular landscape of their tumors.

[Overview of the French Memory Centres healthcare pathway for patients with early Alzheimer disease].

The growing prevalence of the Alzheimer's disease (AD) is an increasing public health concern that led to French recommendations for timely AD diagnosis and patient management as well as a territorial coverage of specialized structures [Memory Centers including Resources and Memory Research Centers (RMRC) and Memory Consultations (MC)]. In view of the potential availability of Disease Modifying Therapies (DMTs), this French observatory aimed to describe the current organization of the Memory Centers, and the care pathway of patients suffering from early AD. Overall, 12 of the 28 RMRC and 44 of the 250 MC solicited by the Federation of Memory Centers participated in this study.

Reappraisal of the fundamental mechanisms of the sHA14-1 molecule as a Bcl-2/Bcl-XL ligand in the context of anticancer therapy: A cell biological study.

Background: HA14-1 is a small-molecule, stable B-cell lymphoma 2 (Bcl-2) antagonist that promotes apoptosis in malignant cells through an incompletely-defined mechanism of action. Bcl-2 and related anti-apoptotic proteins, such as B-cell lymphoma-extra-large [Bcl-XL]), are predominantly localized to the outer mitochondrial membrane, where they regulate cell death pathways. However, the notably short half-life of HA14-1 limits its potential therapeutic application.

Radiation Exposure Analysis on 274 Patients With Vertebral Augmentation Using the Surgivisio Intraoperative Navigation System.

Background: Surgeons' reliance on intraoperative fluoroscopy during vertebroplasty procedures has raised concerns regarding the level of patient and surgeon radiation. Navigation systems have shown a potential to reduce the overall patient and medical staff exposure during dose exposure studies. The main objective of this study was to determine whether the Surgivisio platform (eCential Robotics, France), a unified imaging and navigation platform, lowers the patient dose during routine clinical usage as compared with published fluoroscopy and other navigation options that are published in the literature.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Tau mediates the reshaping of the transcriptional landscape toward intermediate Alzheimer's disease stages.

Introduction: Recent research revealed that Tau plays critical roles in various neuronal functions. We previously demonstrated that destabilization and nuclear delocalization of Tau alter the expression of glutamatergic genes, mediating early neuronal damage.

Methods: In this study, we discovered that changes in Tau availability are linked to global alterations in gene expression that affect multiple neuronal pathways.

The brain in Spain: The legacy of Santiago Ramón y Cajal.

The legacy of Santiago Ramón y Cajal, Spain's first Nobel laureate neuroscientist recognized as the founding father of modern neuroscience, is to be preserved in a new museum in Madrid: the National Museum of Natural Sciences (MNCN), one of the most important scientific research institutes in the country sciences in the scope of natural sciences of the Spanish National Research Council. For a boy who dreamed of being an artist but started his career apprenticed to first a barber and then a cobbler, Santiago Ramón y Cajal made a distinguished mark in science. One of Cajal's most important contributions to our understanding of the brain was his discovery of the direction of the information flow within neurons and in neural circuits, which he called the "dynamic polarization law," without a doubt the founding principle of neurosciences.

Attentes des internes de médecine générale envers leur stage d'observation en pharmacie d'officine.

Objectives: The aim of this study was to collect the expectations of trainees in general practice towards their observation period in a community pharmacy, in order to contribute to a new definition of the objectives of this training period.

Methods: Data were collected using the nominal group technique. The eleven participants were ninth-year general medical students.

Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.

Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.

Hospitalizations with post-traumatic stress disorder in France between 2013 and 2022: a nationwide retrospective study.

Introduction: The lifetime prevalence of PTSD ranges from 6 to 20% and is often associated with comorbid disorders. Despite the significant impact of PTSD, specific data on healthcare utilization related to PTSD remain limited. This study aims to characterize PTSD-related hospitalizations in France over the past decade.

Usefulness of Cerebrospinal Fluid Alzheimer's disease biomarkers in older patients: Evidence from a national multicenter prospective study.

Background: The use of cerebrospinal (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) has been gaining interest in clinical practice. Although their usefulness has been demonstrated, their potential value in older patients remains debated.

Objectives: To assess whether knowledge of the results of CSF AD biomarkers was associated with the same gain in diagnostic confidence in older adults > 80 than in younger patients.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

The Population-Based Incidence and Prevalence of Catatonia.

Objective: Catatonia is a neuropsychiatric disorder that is associated with a range of medical and psychiatric illnesses. Although many single-center studies have been conducted, uncertainty over the population-based incidence and prevalence of the disorder remains. This study reports on the incidence and prevalence rates of catatonia extrapolated from two large epidemiologic studies in the United Kingdom and United States.